Differential activation of adenylyl cyclase by protein kinase C isoenzymes

• Published in: The Journal of biological chemistry 1994-06, Vol.269 (24), p.16554-16558
• Main Authors: KAWABE, J.-I, IWAMI, G, EBINA, T, OHNO, S, KATADA, T, UEDA, Y, HOMCY, C. J, ISHIKAWA, Y
• Format: Article
• Language: English
• Subjects: Adenylyl Cyclases - isolation & purification; Adenylyl Cyclases - metabolism; Amino Acid Sequence; Analytical, structural and metabolic biochemistry; Animals; Antibodies, Monoclonal; Biological and medical sciences; Cell Line; Chromatography, Affinity; Chromatography, DEAE-Cellulose; Colforsin - pharmacology; Enzyme Activation; Enzymes and enzyme inhibitors; Fundamental and applied biological sciences. Psychology; Isoenzymes - biosynthesis; Isoenzymes - isolation & purification; Isoenzymes - metabolism; Kinetics; Lyases; Molecular Sequence Data; Peptide Mapping; Peptides - chemical synthesis; Peptides - immunology; Phosphopeptides - analysis; Protein Kinase C - biosynthesis; Protein Kinase C - isolation & purification; Protein Kinase C - metabolism; Recombinant Fusion Proteins - metabolism; Recombinant Proteins - biosynthesis; Recombinant Proteins - isolation & purification; Recombinant Proteins - metabolism; Transfection
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/s0021-9258(19)89424-3

Cyclic AMP production within cells is altered upon protein kinase C (PKC) activation; however, whether PKC directly modulates adenylyl cyclase (AC) catalytic activity has been controversial. Molecular studies have elucidated the existence of multiple PKC isoenzymes although the functional role of this diversity is not clear. Using purified PKC and AC isoenzymes, we demonstrate that PKC zeta directly phosphorylates type VAC, leading to an approximate 20-fold increase in its catalytic activity, a significantly larger enhancement than that achieved with forskolin (approximately 5-fold), the most potent activator of AC. When forskolin and PKC phosphorylation are combined, type V AC catalytic activity is increased 100-fold over basal levels. The two PKC isoenzymes (alpha and zeta) are additive in their capacity to activate AC, although PKC alpha is less potent than PKC zeta. Our data indicate that PKC can directly and potently regulate AC activity in an isoenzyme-specific manner, suggesting that direct cross-talk plays a major role in coordinating the activity of these two principal signal transduction pathways.